Administration Of High-dose Methylprednisolone Research Articles

Corticosteroid-induced bradycardia following high-dose methylprednisolone administration: a case report

Introduction: Besides their wide use in the clinical field due to their anti-inflammatory and immune-modulating effect, corticosteroids still have a lot of adverse effects. The most common adverse effects are hyperglycemia, hypertension, osteoporosis, psychosis, immunosuppression, weight gain, and hyperlipidemia. Another important side effect is cardiac arrhythmias. Case presentation: We report a case of a 43-year-old woman with multiple sclerosis who developed symptomatic bradycardia after 3 days of treatment with a high dose of methylprednisolone. The patient received a dose of atropine and her bradycardia resolved after 36 h of stopping methylprednisolone. Discussion: While tachyarrhythmias are more common, bradyarrhythmias such as bradycardia and premature atrial or ventricular contraction are rare but crucial to be considered. Conclusion: Corticosteroid-induced bradycardia is usually in sinus rhythm and has an unknown etiology, possibly occurring at high and low doses. The majority of cases in the literature were asymptomatic and resolved spontaneously.

Effect of High Dose Methylprednisolone in Near Hanging Patients: A Retrospective Observational Study in a Tertiary Level Private Hospital in Bangladesh

Background: In the context of Bangladesh, hanging stands out as a notable method of suicide. This study focuses on patients who presented with near hanging, assessing their clinical profile, response to early management protocol and their outcome. Method: Spanning from January 1 to December 31, 2023, this retrospective study delves into the records of 10 Bangladeshi patients who engaged in near hanging. Demographic, clinical, and treatment particulars were collected along with initiation of early management protocol with an emphasis on the administration of high-dose methylprednisolone. The study evaluates the outcomes, including length of stay in the intensive care unit (ICU), and the need for intubation & mechanical ventilation, and in hospital mortality. Results: Within the specified sample size of 10 patients, comprising 30% men with a median age of 18 (range: 14–40), admission data revealed that 20% of patients had a Glasgow Coma Scale of ≤8, 10% exhibited hypotension, and no patient experienced hanging-induced cardiac arrest. All patients received high-dose methylprednisolone to reduce inflammation and oedema in injured spinal cord. Notably, a positive neurological outcome was observed in 90% of patients, with no reported mortality. The median length of stay in the ICU was 3 days, and only 10% of patients required intubation. Conclusion: The administration of high-dose methylprednisolone resulted in favourable outcomes. The study showed a zero-mortality rate, a median ICU stay of 3 days, and a 10% requirement for intubation. These findings emphasize the potential efficacy of high-dose methylprednisolone in managing near hanging cases in the Bangladeshi population, offering insights for future interventions and research. Bangladesh Crit Care J March 2024; 12 (1): 35-40

Effects of grape seed proanthocyanidin extract on side effects of high-dose methylprednisolone administration in male rats.

In this study, we investigated the effects of grape seed proanthocyanidin extract (GSPE) against the side effects of high-dose administration of methylprednisolone (MP) in male rats. A total of 32 adult Wistar male albino rats were divided into four groups: (1) control (CON), received standard food only; (2) MP, received standard food + intraperitoneal injection of 60mg/kg MP on day 7; (3) GSPE, received standard food + 200mg/kg/day GSPE; and (4) MP + GSPE, received standard food + 200mg/kg/day of GSPE + intraperitoneal injection of 60mg/kg MP on day 7. All animals in the GSPE and GSPE + MP groups were treated once a day by oral gavage for 14 consecutive days. The feed intake of rats in the MP and MP + GSPE groups decreased significantly by 24.14% and 13.52%, respectively (p < 0.05). Administration of MP resulted in significant increases in serum concentrations of blood urea nitrogen (p < 0.001), glucose (p < 0.01), alkaline phosphatase, and adrenocorticotropic hormone (p < 0.05). High-dose MP administration significantly reduced catalase (p < 0.001) and glutathione peroxidase (p < 0.05) concentrations in the liver and kidney tissues of rats, while glutathione concentrations were only reduced in liver tissue (p < 0.05). The expression levels of Bcl-2 and TNF-α in liver, kidney, and testicular tissue were significantly increased, while the expression levels of caspase-3 were reduced (p < 0.001). Furthermore, sperm concentration was significantly affected by GSPE in rats induced by high-dose MP, and sperm loss was significantly reduced in MP + GSPE (p < 0.05). These findings suggest that GSPE could be useful as a supplement to alleviate MP-induced toxicity in rats.

Challenges in administering immunosuppressive therapy in severe bacterial infection interfering crisis and refractory childhood systemic lupus erythematosus

Background: Childhood Systemic Lupus Erythematosus (cSLE) mostly come with severe manifestation compared to the adult. Infection aggravated the multisystem inflammation and interfering immunosuppressive agent protocol. Case: A 12-year-old girl was hospitalized for a month with massive edema and fever after being diagnosed with nephrotic syndrome and taken prednison for four weeks. The patient was completely bedridden, presented with hypertension, large erythematous striae across the trunk and limbs, and darkened skin. Further evaluation showed the EULAR/ACR classification criteria for SLE with score of 26. Cellulitis was suspected when a red, pinprick-sized papule appeared on the patient's right leg be increased significantly in size within two hours. Following the collection of a wound culture and blood culture specimen, triple antibiotics were given. Seven days after the wound has healed, administered of cyclophosphamide was started. Cyclophosphamide is used as an emergency treatment for lupus crises, as she experienced seizure and delirium. Seven days after cyclophosphamide administration, the wound was revived. Initial blood and wound cultures indicated an infection caused by Serratia marcescens; however, the second wound culture revealed infections caused by Klebsiella oxytoca and Enterobacter cloacae. We commenced Meropenem based on a sensitivity test to establish protection for the following administration of high-dose methylprednisolone with rituximab and cyclophosphamide. The lupus crisis was precipitated by an infection-induced inflammatory response. On day 17, after the calf and back wounds were completely healed, the antibiotic was withdrawn. In order to protect organ functionality, physiotherapy and nutritional support were employed. Conclusion: Clinicians need to be mindful and closely observe patient with severe SLE accompanied with infection to balancing intervention for immunosuppressant therapy and antibiotic.

Encephalomyelitis associated with coronavirus disease 2019: a case report

BackgroundDespite a considerable number of articles regarding neurological manifestations associated with severe acute respiratory syndrome coronavirus 2 infection, reports on transverse myelitis and encephalitis are scarce.Case presentationWe report a 35-year-old Asian Arab female presenting with longitudinally extensive transverse myelitis within 3 weeks after being diagnosed with mild coronavirus disease 2019 infection. Administration of high-dose methylprednisolone led to significant clinical improvement. However, 2 days after discharge, the patient was readmitted with encephalitis manifestations, consisting of fever and loss of consciousness, along with deterioration in myelitis symptoms. Severe acute respiratory syndrome coronavirus 2 antibody was detected in cerebrospinal fluid, but DNA of severe acute respiratory syndrome coronavirus 2 was not found. Clinical recovery was achieved after the administration of intravenous immunoglobulin.ConclusionLongitudinally extensive transverse myelitis can be a neurological manifestation of coronavirus disease 2019 and can be followed by encephalomyelitis episodes. High-dose steroids and intravenous immunoglobulin as an immunomodulator are possible effective treatment options.

Alemtuzumab induced hemodynamic change in relapsing multiple sclerosis occurs independent of corticosteroid premedication – a retrospective multicentre study

Background Alemtuzumab (ATZ), a highly effective disease modifying treatment for relapsing multiple sclerosis (MS), is associated with the rare risk of intracerebral hemorrhage. Increase of blood pressure (BP) was hypothesized to be causative, but prior administration of high-dose methylprednisolone (HDMP) is a potential confounder.Objective To analyze BP change in MS patients treated with ATZ and prior HDMP treatment compared to patients receiving HDMP only for acute relapse.Methods In this retrospective study, 30 patients treated with ATZ/HDMP and 60 age-, sex- and disability-matched controls treated with HDMP were included. Primary endpoint was the change of systolic BP (SBP) between before ATZ cycle and the maximum value measured during the treatment cycle; secondary endpoints were change in diastolic BP (DBP) and heart rate (HR).Results Change of SBP observed in ATZ/HDMP treated patients was significantly higher than in HDMP controls (mean maximal change of 12.8 vs. 8.1 mmHg, p = 0.033). An increase of SBP exceeding 20% from baseline was observed in 5 (16.7%) patients on ATZ/HDMP compared to 3 (5.0%) on HDMP (p = 0.078). The day after the 1st ATZ infusion, mean HR was higher in the ATZ/HDMP group compared to HDMP controls (82.5 vs. 73.2 bpm, p = 0.005), although there was no significant group difference over time.Conclusions ATZ treatment induced a slight, but significant increase in SBP independent of HDMP. Although hemodynamic alterations alone seem unlikely as putative mechanism for cerebral bleedings, strict cardiovascular monitoring is recommended to reduce rare, but severe cardiovascular side effects.

Administration of High-Dose Methylprednisolone Worsens Bone Loss after Acute Spinal Cord Injury in Rats.

The administration of high-dose methylprednisolone (MP) for 24–48 h after traumatic spinal cord injury (SCI) has been shown to improve functional recovery. The known adverse effects of MP on skeletal muscle and the immune system, though, have raised clinically relevant safety concerns. However, the effect of MP administration on SCI-induced bone loss has not been evaluated to date. This study examined the adverse effects of high-dose MP administration on skeletal bone after acute SCI in rodents. Male rats underwent spinal cord transection at T3–T4, which was followed by an intravenous injection of MP and subsequent infusion of MP for 24 h. At 2 days, animals were euthanized and hindlimb bone samples were collected. MP significantly reduced bone mineral density (−6.7%) and induced deterioration of bone microstructure (trabecular bone volume/tissue volume, −18.4%; trabecular number, −19.4%) in the distal femur of SCI rats. MP significantly increased expression in the hindlimb bones of osteoclastic genes receptor activator of nuclear factor-κB ligand (RANKL; +402%), triiodothyronine receptor auxiliary protein (+32%), calcitonin receptor (+41%), and reduced osteoprotegerin/RANKL ratio (−72%) compared to those of SCI-vehicle animals. Collectively, 1 day of high-dose MP at a dose comparable to the dosing regimen prescribed to patients who qualify to receive this treatment approach with acute SCI increased loss of bone mass and integrity below the level of lesion than that of animals that had SCI alone, and was associated with further elevation in the expression of genes involved in pathways associated with osteoclastic bone resorption than that observed in SCI animals.

Acute Disseminated Encephalomyelitis

Absrtract Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory demyelinating disorder of the central nervous system that predominantly affects the pediatric population, and it is characterized by an acute or subacute onset of multifocal neurological symptoms. ADEM is typically a monophasic illness, and the majority of cases are associated with either a preceding infection or vaccination. First-line therapy for the disease is intravenous administration of high-dose methylprednisolone, and the long-term prognosis of ADEM is generally favorable.

Therapeutic regimens and factors associated with mortality in patients with severe COVID-19 infection treated at the Hospital Nacional Alberto Sabogal Sologuren, 2020

Objective: To explore the therapeutic regimen and factors associated with mortality in patients with severe COVID-19 infection treated at the Hospital Nacional Alberto Sabogal Sologuren in 2020. Materials and methods: An observational, case-control, analytical and prospective study conducted in patients with severe COVID-19 infection at hospital admission between June and September 2020. The study population was classified into two groups: case group (61 deceased patients) and control group (60 discharged patients). Data were analyzed using Stata statistical software. Bivariate and multivariate logistic regression analyses were performed with a 95 % confidence level. Results: As for patients with severe COVID-19 infection, ages older than 60 years are associated with mortality (p = 0.035; OR = 2.21; CI: [1.05 – 4.63]). Different therapeutic regimens were included in the research: patients who received high-dose methylprednisolone had more probability of dying compared to those who received other corticosteroids (p = 0.001; adjusted OR = 5.18; CI: [1.94 – 13.83]). Patients who were treated with azithromycin for more than five days had more probability of dying compared to those that took it for fewer days (p = 0.000; adjusted OR = 7.14; CI: [2.22 – 22.99]). The multivariate model showed a 73.06 % predictive probability of mortality for patients with severe COVID-19 infection. Conclusions: The therapeutic regimens that include the administration of high-dose methylprednisolone and azithromycin for more than five days increase the probability of dying in patients with severe COVID-19 infection. Furthermore, ages over 60 years were associated with mortality in the patients who participated in the study.

Intravenous immunoglobulin accompanied with high-dose methylprednisolone therapy for 17 children with anti-N-methyl-D-aspartate receptor encephalitis: Clinic and nursing

ObjectiveAn increasing number of pediatric patients are being diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, whose treatment requires immunotherapy through nursing interventions. This study aimed to analyze the clinical features and long-term prognosis of pediatric anti-NMDAR encephalitis and to gather nursing experiences of immunotherapy. MethodsSeventeen children diagnosed with anti-NMDAR encephalitis were admitted to the pediatric department. They were subjected to a therapy of intravenous immunoglobulin (IVIG) accompanied with high-dose methylprednisolone (HDMP). Multidisciplinary cooperation and intensive care were used to manage them. The effects of nursing intervention and therapy were repeatedly assessed and analyzed throughout the course of treatment and recovery. ResultsNone of the patients manifested adverse drug reaction (ADR) during IVIG administration. At the first administration of HDMP, ADRs were promptly and efficiently treated in four patients (24%; i.e., one case each of hyperglycosemia, hypertension, aggravated symptoms, and gastrointestinal bleed). Two patients underwent rehabilitation, and six patients received hyperbaric oxygenation during hospitalization. Nine patients with indwelling gastric tubes experienced four times of unplanned extubation. Hospital stay ranged from 11 days to 59 days, with the mean duration of 26 days. Discharge evaluation revealed that 16 patients who scored 0–2 on the modified Rankin scale presented obvious remission, and one patient who had a mRS score of 4 exhibited less improvement. The mRS scores of hospitalization, discharge, and six-month follow-up displayed statistically significant differences. ConclusionsNursing interventions of immunotherapy ensures the security of IVIG administration. Multidisciplinary cooperation promotes remission. Our findings can serve as reference for healthcare teams.

Interstitial pneumonia in a patient treated with TAS-102 for metastatic colorectal cancer: a case report

BackgroundTAS-102, a new treatment option for patients with metastatic colorectal cancer that is refractory or intolerant to standard therapies, has been improving survival with acceptable tolerability and adverse events. Adverse hematological events associated with TAS-102 treatment were extensively profiled in the RECOURSE trial, but pulmonary toxicities associated with TAS-102 therapy are distinctly uncommon. In a recent early post-marketing phase vigilance on TAS-102 in Japan, seven cases of pulmonary disease were reported, but patient follow-up in this study was incomplete. Here, we present the first case of interstitial lung disease occurring in association with TAS-102 treatment.Case presentationA 57-year-old Japanese man who had previously received two standard treatments was admitted in 2014, at which time we administered TAS-102 (110 mg/day) as a third-line chemotherapy. He was safely treated with TAS-102 for the first planned cycle; however, approximately 4 days after receiving the second cycle of TAS-102, he complained of high fever and subsequent dyspnea with severe hypoxemia and went to the emergency room. A chest X-ray revealed diffuse coarse reticular shadows with ground-glass opacity on both lungs. Furthermore, a chest computed tomography scan showed thickening of the bronchovascular bundles with extensive ground-glass opacification and pleural effusions in both lung fields.In addition, a peripheral blood lymphocyte stimulation test with TAS-102 showed higher values compared with control samples. Consequently, we suspected drug-induced interstitial pneumonia, and discontinued treatment. Our patient was given an initial administration of high-dose methylprednisolone (1000 mg/day) for 3 days and oxygen. Our patient was discharged with oral prednisolone (20 mg/day) and improved symptomatically and radiologically.ConclusionsThese findings suggest that interstitial pneumonia is a rare complication of TAS-102 chemotherapy, but the possibility of interstitial pneumonia should always be considered when a patient presents with a respiratory disorder while undergoing TAS-102 systemic chemotherapy.Prompt discontinuation of TAS-102 and treatment with high-dosage corticosteroids is needed to avoid exacerbating respiratory symptoms.

High-Dose Methylprednisolone to Prevent Platelet Decline in Preeclampsia: A Randomized Controlled Trial.

To evaluate whether early administration of high-dose methylprednisolone limits the fall of platelets in preeclampsia. A randomized trial of 180 mg methylprednisolone or placebo administered in divided doses over 36 hours was conducted in women admitted for preeclampsia and platelet counts below 150×10/L in four French academic centers. Patients were not included when platelet counts were below 50×10/L or when immediate delivery was required. The primary study outcome was the proportion of patients with platelet counts above 100×10/L 36 hours after the first dose of study medication. The total sample size needed to detect a 23% difference in the rate of this outcome between groups with a one-tailed α of 0.05 and 90% power was 94 patients. Thirty-six patients were randomly assigned to receive methylprednisolone and 34 placebo between October 2007 and May 2011. Platelet counts above 100×10/L at 36 hours after the first dose of study medication were recorded in 30 (83%) in the active group and 29 (85%) in the placebo group (relative risk 0.98, 95% confidence interval 0.80-1.20; P=.82). The only adverse potentially study-related event was hyperglycemia in one woman allocated to methylprednisolone. In women with preeclampsia and platelet counts under 150×10/L, methylprednisolone was not effective in maintaining platelet counts above 100×10/L. EU Clinical Trials Register, http://clinicaltrialsregister.eu, EudraCT 2006-004881-15-FR.

Posturography in MS patients treated with high dose methylprednisolone

Objectives: To evaluate the sensitivity of the balance sway index (SI) to drug-induced functional changes during acute relapse in patients with MS.Methods: Dynamic posturography was used to derive the SI in 11 healthy subjects and 13 MS patients before and after intravenous high dose methylprednisolone (HDMP).Results: In both groups, SI was lower in the least demanding task and increased with test complexity. Compared to the healthy group, patients were distinguished by a higher SI both prior to and following administration of HDMP (p < 0.008). However, the effect of the drug on patients’ SI was unremarkable. Total Expanded Disability Status Scale score was lower after treatment compared to pre-treatment values (p < 0.001), with significantly lower mean score recorded in patients with pyramidal and cerebellar abnormalities (p = 0.017 and p = 0.011, respectively).Discussion: The SI measure of dynamic posturography is not sensitive to short-term HDMP-induced functional changes during acute relapse in patients with MS. Further studies are needed to evaluate modified balance protocols and the possible long-term treatment effects of HDMP on SI.

Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial

High doses of intravenous methylprednisolone are recommended to treat relapses in patients with multiple sclerosis, but can be inconvenient and expensive. We aimed to assess whether oral administration of high-dose methylprednisolone was non-inferior to intravenous administration. We did this multicentre, double-blind, randomised, controlled, non-inferiority trial at 13 centres for multiple sclerosis in France. We enrolled patients aged 18-55 years with relapsing-remitting multiple sclerosis who reported a relapse within the previous 15 days that caused an increase of at least one point in one or more scores on the Kurtzke Functional System Scale. With use of a computer-generated randomisation list and in blocks of four, we randomly assigned (1:1) patients to either oral or intravenous methylprednisolone, 1000 mg, once a day for 3 days. Patients, treating physicians and nurses, and data and outcome assessors were all masked to treatment allocation, which was achieved with the use of saline solution and placebo capsules. The primary endpoint was the proportion of patients who had improved by day 28 (decrease of at least one point in most affected score on Kurtzke Functional System Scale), without need for retreatment with corticosteroids, in the per-protocol population. The trial was powered to assess non-inferiority of oral compared with intravenous methylprednisolone with a predetermined non-inferiority margin of 15%. This trial is registered with ClinicalTrials.gov, number NCT00984984. Between Jan 29, 2008, and June 14, 2013, we screened 200 patients and enrolled 199. We randomly assigned 100 patients to oral methylprednisolone and 99 patients to intravenous methylprednisolone with a mean time from relapse onset to treatment of 7·0 days (SD 3·6) and 7·4 days (3·9), respectively. In the per-protocol population, 66 (81%) of 82 patients in the oral group and 72 (80%) of 90 patients in the intravenous group achieved the primary endpoint (absolute treatment difference 0·5%, 90% CI -9·5 to 10·4). Rates of adverse events were similar, but insomnia was more frequently reported in the oral group (77 [77%]) than in the intravenous group (63 [64%]). Oral administration of high-dose methylprednisolone for 3 days was not inferior to intravenous administration for improvement of disability scores 1 month after treatment and had a similar safety profile. This finding could have implications for access to treatment, patient comfort, and cost, but indication should always be properly considered by clinicians. French Health Ministry, Ligue Française contre la SEP, Teva.

Effects of Methylprednisolone on Femoral Bone Marrow: Age-Dependent Susceptibility

We aimed to test our primary hypothesis that the effects of methylprednisolone on bone marrow in chickens are age-sensitive and increase with prolonged treatment and our secondary hypothesis that the effects of methylprednisolone on bone marrow can have individual effects. Sixteen control (group A) and 29 methylprednisolone-treated (group B) chickens were categorised by age: pubertal chicks (subgroups A1, B1), young hens (A2, B2), and adult hens (A3, B3). Histologic evaluation 12 to 50 weeks after the start of methylprednisolone treatment included fat cell proliferation, trabecular bone loss, necrosis of bone and marrow, and new bone formation in the femoral head, neck, and intertrochanteric area. There were significant differences between groups A1 and B1 in new bone formation in the femoral neck (P = 0.048) and fat cell proliferation in the femoral head (P = 0.008) and neck (P = 0.048). New bone formation in the femoral head was also significantly different (P = 0.023) between groups A2 and B2. No differences were noted between groups A3 and B3 (all P>0.05). Necrosis of bone and marrow was observed in four control and three methylprednisolone-treated chickens (P>0.05). Significant new bone formation and fat cell proliferation in pubertal and young chickens occurred 12 to 19 weeks after administration of high-dose methylprednisolone. Younger animals may be more susceptible to methylprednisolone, and responses to methylprednisolone in femoral marrow may vary among individuals.

Hormonal and histological changes in the ovaries with high-doses of methylprednisolone administration for acute spinal cord injury: An experimental study

This study was conducted to investigate the hormonal and histological changes in the ovaries with high doses of methylprednisolone administration for acute spinal cord injury (SCI). Group I (trauma group, eight rats) were subjected to laminectomy and SCI but received no treatment. Group II (steroid group, eight rats) were subjected to SCI and received methylprednisolone (30 mg/kg, intraperitoneally). Group III (control group, six rats) underwent a sham operation without trauma and treatment. Malondialdehyde (MDA) levels were significantly decreased in Group II (p < 0.05). The scores of histopathological damage of the ovaries in the three groups were found to be statistically comparable (p > 0.05). Serum anti-Müllerian hormone (AMH) levels in the steroid group was significantly lower compared with the control group (p < 0.05). High-dose methylprednisolone administration may effect ovarian reserve with reversible ovarian damage and can resolve lipid peroxidation in rats with spinal cord injury.

Response to ‘The administration of high-dose methylprednisolone for 24 h reduced muscle size and increased atrophy-related gene expression in spinal cord-injured rats’

Response to ‘The administration of high-dose methylprednisolone for 24 h reduced muscle size and increased atrophy-related gene expression in spinal cord-injured rats’

A review: the role of high dose methylprednisolone in spinal cord trauma in children

The use of steroids in traumatic spinal cord injury (SCI) in children is controversial. There is a paucity of literature on its usage. To help clarify recommendations on steroid use in children, we reviewed the current literature on the administration of high dose methylprednisolone (MP) use in traumatic spinal cord injuries with an emphasis in pediatric spinal cord trauma. A retrospective review of the current literature on traumatic spinal cord injuries was conducted. Outcomes were critically reviewed from the National Acute Spinal Cord Injury Studies (NASCIS) II and III and Cochrane review; as well as, other randomized and retrospective studies. Papers describing objective neurological outcomes were only included. The outcomes of neurological improvement following steroid infusion have not been reproducible outside of the NASCIS and one single Japanese trial. High dose steroids significantly increase the risk of infections leading to prolonged hospital stay and ventilator dependence. Data from adult studies remains controversial with insufficient data to support administration of MP for treatment of traumatic spinal cord injuries. Randomized controlled trials are needed in the pediatric population to assess the advantages of steroid use after SCI in children. On the basis of the current evidence, the use of steroids in patients is associated with increased infectious risks and no neurological improvements.

Fatal interstitial pneumonia associated with oxaliplatin-based therapy in a patient with metastatic rectal cancer.

Oxaliplatin in combination with 5-fluorouuacil and leucovorin (FOLFOX) is one of the most commonly used first-line chemotherapies for patients with advanced or metastatic colorectal cancer. Pulmonary toxicity, including interstitial pneumonia (IP)/peumonitis, is a very rare complication. We report a case of fatal IP associated with FOLFOX therapy in a patient with metastatic rectal cancer. A 74-year-old man with rectal adenocarcinoma and associated liver metastases underwent palliative surgery and 21 cycles of modified FOLFOX6 therapy. After starting the 22nd therapy cycle, the patient developed a high fever with non-productive cough. Chest X-ray demonstrated diffuse ground-glass opacities in both lungs, and computed tomography showed severe disorder of the bilateral lung architecture. On the basis of a lymphocyte stimulation test (DLST), oxaliplatin-induced IP was diagnosed. Intravenous administration of high-dose methylprednisolone was started, but the symptoms and radiological findings were not improved. The patient died of respiratory failure 16days after the last administration of oxaliplatin. Although IP is a rare but potentially fatal complication of oxaliplatin-based treatment in colorectal cancer patients, clinicians should pay careful attention to the clinical respiratory symptoms and radiographic findings in colorectal cancer patients receiving FOLFOX therapy.

The administration of high-dose methylprednisolone for 24 h reduced muscle size and increased atrophy-related gene expression in spinal cord-injured rats

Administration after spinal cord injury (SCI) of methylprednisolone (MP) for 24-48 h has been suggested to improve functional outcome. The safety of this approach has been questioned because of the known adverse effects of glucocorticoids on skeletal muscle and the immune system. The purpose of this study was to explicitly test adverse effects of regimen of MP administration on skeletal muscle. Male rats underwent spinal cord transection at T9-T10, followed by an intravenous injection of MP and subsequent infusion of MP for 24 h. MP significantly reduced the weight of the triceps, soleus, plantaris and gastrocnemius muscles, with the greatest effect being a 63% decrease in triceps weight (for example, muscle above the level of lesion) at 7 days; below the level of lesion, gastrocnemius weight was reduced by 33% by SCI alone, and by 45% by SCI and MP. Centralized nuclei were found in myofibers of the gastrocnemius and triceps from the MP-SCI group, but not other groups. MP increased expression in the triceps, soleus and plantaris of FOXO1, MAFbx, MuRF1 and REDD1 at 1 day, and, in plantaris, at 7 days. Thus, 1 day of MP at a dose comparable to those routinely employed in clinical practice immediately after SCI resulted in marked atrophy of functionally intact muscle above the level of lesion, and worsened atrophy of paralyzed muscle below the level of lesion, associated with elevations in expression of four genes involved in pathways associated with muscle atrophy.